(1) Field of the Invention
The present invention relates to a process for the preparation of protected 3-amino-1,2-dihydroxypropane acetal, particularly in chiral forms, for use as an intermediate in the preparation of various 3-carbon compounds which are chiral. In particular, the present invention relates to the process for preparation of 3-amino-1,2-dihydroxypropane isopropylidene acetal. The invention is particularly useful for preparation of glycidol, 1-bromo-2,3-dihydroxypropane, or 3-amino-1,2-dihydroxypropane starting from 3-hydroxy-.gamma.-butyrolactone.
(2) Background of the Invention
Chiral 3-carbon synthons are very important compounds because they are used in a variety of pharmaceuticals and material science applications ranging from beta-blocker drugs, phospholipid and glycolipid analogs, thromboxane synthase inhibitors, sulfolipids and liquid crystal materials. However, chiral 3-carbon synthons are extremely expensive. Three key 3-carbon building blocks are (R)-glycidol (2), (R)-1-bromo-2,3-dihydroxypropane (3) and (S)-3-amino-1,2-dihydroxypropane (4). ##STR1##
(R)-glycidol (2) and its (S)-isomer are much used intermediates in the synthesis of chiral compounds. Because of this, much effort has been expended in developing routes to them. These include catalytic oxidations with peroxides and chiral transition metal complexes (Byun, H. -S, et al., J. Org. Chem. 59:668-671 (1994)), enzymatic resolutions of racemic esters using lipases to selectively deacylate one member enantiomer (Bednarski, M. D., et al., J. Am. Chem. Soc. 109:1283-1285 (1987); Fuganti, C., et al., Tetrahedron 44:2575-2582 (1988); and Chen, J., et al., Tetrahedron Lett. 34:7663-7666 (1993)), and treatment of a chiral 1,2-propane diol with a leaving group such as a halide or tosylate ester in the 3-position with base (Baldwin, J. J., et al., J. Med. Chem. 25:931-936 (1982)). The availability of an easy route to 3 is therefore de facto a route to 2. The aminodiol 4 is a substructure that appears in a large class of important drugs especially the .beta.-blockers such as Propanalol (5) and Metoprolol (6), the antiviral agent (7) and the thromboxane synthase inhibitor (8). ##STR2##
Thus, there is a need for a process to make chiral 3-carbon synthons which is inexpensive, safe, and easy to perform. In particular, it is desirable to have a process for making chiral 3-carbon synthons from renewable natural resources.